A FASEB Summer Conference titled "Biology of Calpains in Health and Disease" is scheduled for June 12-17, 2004. The meeting will be held in Tuscon, Arizona. This will be the third FASEB-sponsored Calpain meeting. Funds are being requested from three NIH divisions (NIAMS, NIDDK and NEI) in partial support of this conference. The thematic sessions for the conference will be: 1) Calpain Gene Family, 2) Calpain Structure, 3) Physiological Roles, 4) Calpains and Signal Transduction, 5) Pathologic Involvement of Calpains, 6), Calpain Inhibitors in Treatment of Disease, 7) Agricultural Applications and 8) A Holistic View (two sessions). The latter session (A Holistic View) is designed to stimulate thoughts on how the calpains participate, in tandem with other proteases, in mediation of normal and pathological processes (e.g., apoptosis and myofibrillar protein degradation). This topic will be supported by a keynote speaker who is a leader in the biology of cysteine proteases (Dr. Alan Barrett, Babraham Institute) and by speakers who have expertise with other proteolytic systems (notably the ubiquitin/proteasome system). A meeting on the biology of the calpains is highly-relevant to the NIH because calpains are involved in both normal and pathologic processes. The activities of the house-keeping u- and m-calpains are important to normal turnover and processing of cytoskeletal and membrane proteins in all tissues. A defective muscle-specific calpain (p94) is responsible, in part, for Limb-Girdle Muscular Dystrophy Type IIA. Interestingly, the gene encoding p94 is also expressed as a lens-specific calpain isoform (Lp82) which, when activates, underlies cataractogenesis. Defects in calpain-10 have now been related to adult onset diabetes and to cystic ovary disease. Skeletal and cardiac muscle damage as well as cerebral ischemia have been related to pathologic activation of calpains. Three years will have passed since the last meeting on calpains. Substantial progress on the genomics, biology, structure, activation and roles of calpains has been made in the past few years. The proposed program will provide the forum by which the momentum in this field may be maintained.